Calcium-activated potassium and voltage-gated calcium channels participate in an intimate interplay in excitable cells, by which each kind of channel regulates the function of the other. The calcium that enters a cell through voltage-gated calcium channels activates nearby calcium-activated potassium channels that in turn hyperpolarize the cell arid cause calcium channels to shut. This functional coupling plays important roles in determining electrical excitability and influencing signaling events in neurons and muscle cells. In order for the channels to interact functionally, they must be localized close together. Furthermore, in a cell expressing multiple types of each channel, functional coupling is often channel type specific. The work proposed here is designed to determine the mechanisms by which functional coupling is achieved, including the molecular components necessary for channel association and the determinants of channel type specificity. The results will contribute to our understanding of the physiology of processes such as the regulation of neurotransmitter release and the determination of smooth muscle tone. Such information could lead to useful strategies for the treatment and/or prevention of neurological and vascular diseases of the central nervous system.